Malaria during pregnancy leads to many deaths in Africa. COVID-19 contributed to more malaria cases due to interruptions in prevention efforts. Intermittent presumptive treatment (IPTP) is an effective malaria prevention strategy for pregnant women, but adoption barriers still exist. The study aim was to explore barriers to the adoption of IPTP at Kawempe National Referral Hospital (KNRH) Uganda. In a qualitative study design, data was collected using focus group discussions. A total of 37 postpartum mothers were interviewed in six focus group discussions. The interviews were conducted using a structured guide to explore barriers to IPTP implementation at KNRH. The data was transcribed, coded, and analysed using NVivo 10. The study found that mothers lacked adequate knowledge about IPTP, faced socioeconomic and cultural constraints, fear of side effects, a high pill burden, and experience of health system challenges as major themes of barriers to optimal IPTP use. Challenges in the service delivery and inadequate information in regard to importance and expected side effects were identified by the users as the major barriers to IPTP delivery in public health care setting. Improving delivery of focused health education talks and health work attitude and delivery chain for IPTP in the health facilities are recommended to increase its uptake.